In our attempt to determine the molecular mechanism involved in calcium-dependent secretion, we have developed a model based on the opening of anion channels-and calcium-activated cation channels present in secretory vesicles. One test of this model is whether these channels are, in fact, present in vesicles, and we have now shown that the secretory vesicles of bovine neuro-hypophysis cells contain anion channels. We also have preliminary evidence that they contain calcium-activated cation channels. Another test of this model is whether or not secretion is correlated with the opening of these vesicle channels. In particular, we are testing this in bovine parathyroid cells, where secretion has a unique dependence on calcium concentration. We have completed patch-clamp experiments which show that these calls contain calcium-activated potassium channels of an unusual type. These channels tend to open when the internal calcium concentration is increased above about 50 nM and to close when the internal calcium concentration is increased above about 150 nM. We have also found that parathormone secretion from these cells has the same type of dependence on internal calcium concentration. This correlation supports the basic idea of our channel model for secretion.